Capillary filtration coeficient, CFC, measures the filtration ability of a whole organ capillary bed. The accepted view for skeletal muscle is that CFC is controlled mainly by changes in the tone of precapilary smooth muscle, which is regulated in turn by the local metabolic environment. However, many investigators, including ourselves, cannot reproduce some or all of the findings which led to the metabolic control hypothesis. It is proposed to investigate the causes of the divergence in results and/or interpretation using the isolated perfused cat hindlimb. The principal experimental differences are 1) whole blood vs. low hematocrit perfusates, 2) the presence or absence of the animal in the perfusion circuit, 3) constant pressure vs. constant flow perfusion, and, perhaps the most important, 4) the method of determining CFC. CFC is determined by calculating a rate of weight increase at some variable, and frequently undefined, time following a step increase in venous pressure. But, as the rate of weight increase falls with time (for reasons which are mainly unknown in well-hydrated, maximally-vasodilated skeletal muscle), the period chosen in which to measure the rate of weight increase is critical. In addition to studying the factors listed above, it is proposed to investigate why the rate of weight increase varies with time using the same preparation. By the use of perfusates with differing protein concentrations and other factors, the possible role of protein in the fall of the rate of weight increase will be studied. In addition, as one group has proposed that the decreasing rate is caused by a low compliance tissue compartment, this hypothesis will be tested by using different rates of filtration and different hydration states with low protein perfusates and stop-flow techniques. These proposed experiments will resolve many of the differences described above, and will significantly improve our understanding of the nature of filtration at the capillary wall, a very basic and illunderstood process in microcirculatory physiology. Such knowledge will aid the treatment of such disorders as edema and circulatory shock.